GEO series

In Vivo Tumor Growth Control by General Control Nonderepressible 2 (GCN2) Targeting Agents Results from Kinase Activation

GSE297227 Homo sapiens (human) RNA-seq (gene expression) 59 samples Submitted 2025/06/30 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 59 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 59 samples: 7 conditions, mostly with about 9 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

The objective of this study was to determine the therapeutic effect and PK/PD relationship of Hibercell compound HC-7366 after 3 days continuous BID dosing (7 administrations) in the MOLM-16 subcutaneous leukemia xenograft model. Single point plasma concentrations were determined 1 h post dose on day 4. HC-7366 at dose levels of 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg BID dosing all exhibited significant antitumor activities with TGI% values of 74.8%, 91.5%, 93.6%, 82.0%, and 62.0% (P values < 0.05 vs.

Read the full summary ↓

vehicle control group), respectively. The maximum antitumor effects were achieved at 3 mg/kg which resulted in Partial Response (PR, ≥50% tumor regression) in 100% of animals. The plasma concentrations of HC-7366 at 1 h post dose on day 4 provided a single point determination of systemic exposure. The concentrations increased in approximate proportion to dose level across the range 0.3 – 30 mg/kg. These data indicate that HC-7366 treatment exhibits a ‘U-shaped’ dose/exposure-response relationship in this model when dosed at 0.3, 1, 3, 10 or 30 mg/kg, orally (PO), twice per day (BID). Regarding the safety profile, most animals treated with HC-7366 at dose level of 1 mg/kg and 3 mg/kg showed minor to moderate BW loss during the study period. IHC on these samples demonstrated maximal induction of the ATF4 targets ASNS, PSAT1 and PHGDH at 1 and 3 mg/kg doses, with 0.3, 10 and 30 have smaller increases over vehicle. RNA-Seq confirmed that the ASNS, PSAT1 and PHGDH effects were regulated at the mRNA level in the U-shaped manner. DDIT3, BBC3, and ATF4 mRNA also demonstrated a U-shaped upregulation, with maximal effect at 3 mg/kg. Notably, PPP1R15A, MCL1, PPP1R15B, EIF2AK4, CASP3, and EIF2S1 mRNA showed much more modest regulation. These data strongly suggest that HC-7366 is having its maximal efficacy in MOLM-16 when it is behaving as a GCN2 activator (i.e., at 1 and 3 mg/kg), where higher concentrations begin to inhibit this effect (at 10 and 30 mg/kg).

This dataset

Open GSE297227 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE297227_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1263206 and SRA study SRP585682. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

7 conditions, mostly with about 9 replicates each

Vehicle ×9 HC-7366 0.3 mg/kg ×9 HC-7366 1 mg/kg ×9 HC-7366 3 mg/kg ×9 HC-7366 10 mg/kg ×9 HC-7366 30 mg/kg ×9 Basal Tumo ×5

Supports a between-group comparison across 59 samples.

How we read this: 7 replicated groups read from 59 sample titles; they account for 59 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8986500 Vehicle 27 Vehicle
GSM8986501 Vehicle 37 Vehicle
GSM8986502 Vehicle 59 Vehicle
GSM8986503 Vehicle 72 Vehicle
GSM8986504 Vehicle 75 Vehicle
GSM8986505 Vehicle 117 Vehicle
GSM8986506 Vehicle 124 Vehicle
GSM8986507 Vehicle 186 Vehicle
GSM8986508 Vehicle 199 Vehicle
GSM8986509 HC-7366 0.3 mg/kg 43 HC-7366 0.3 mg/kg
GSM8986510 HC-7366 0.3 mg/kg 78 HC-7366 0.3 mg/kg
GSM8986511 HC-7366 0.3 mg/kg 96 HC-7366 0.3 mg/kg
GSM8986512 HC-7366 0.3 mg/kg 108 HC-7366 0.3 mg/kg
GSM8986513 HC-7366 0.3 mg/kg 151 HC-7366 0.3 mg/kg
GSM8986514 HC-7366 0.3 mg/kg 157 HC-7366 0.3 mg/kg
GSM8986515 HC-7366 0.3 mg/kg 182 HC-7366 0.3 mg/kg
GSM8986516 HC-7366 0.3 mg/kg 187 HC-7366 0.3 mg/kg
GSM8986517 HC-7366 0.3 mg/kg 198 HC-7366 0.3 mg/kg
GSM8986518 HC-7366 1 mg/kg 25 HC-7366 1 mg/kg
GSM8986519 HC-7366 1 mg/kg 30 HC-7366 1 mg/kg
GSM8986520 HC-7366 1 mg/kg 48 HC-7366 1 mg/kg
GSM8986521 HC-7366 1 mg/kg 52 HC-7366 1 mg/kg
GSM8986522 HC-7366 1 mg/kg 55 HC-7366 1 mg/kg
GSM8986523 HC-7366 1 mg/kg 130 HC-7366 1 mg/kg
GSM8986524 HC-7366 1 mg/kg 135 HC-7366 1 mg/kg
GSM8986525 HC-7366 1 mg/kg 162 HC-7366 1 mg/kg
GSM8986526 HC-7366 1 mg/kg 193 HC-7366 1 mg/kg
GSM8986527 HC-7366 3 mg/kg 107 HC-7366 3 mg/kg
GSM8986528 HC-7366 3 mg/kg 119 HC-7366 3 mg/kg
GSM8986529 HC-7366 3 mg/kg 122 HC-7366 3 mg/kg
GSM8986530 HC-7366 3 mg/kg 129 HC-7366 3 mg/kg
GSM8986531 HC-7366 3 mg/kg 164 HC-7366 3 mg/kg
GSM8986532 HC-7366 3 mg/kg 176 HC-7366 3 mg/kg
GSM8986533 HC-7366 3 mg/kg 179 HC-7366 3 mg/kg
GSM8986534 HC-7366 3 mg/kg 185 HC-7366 3 mg/kg
GSM8986535 HC-7366 3 mg/kg 197 HC-7366 3 mg/kg
GSM8986536 HC-7366 10 mg/kg 24 HC-7366 10 mg/kg
GSM8986537 HC-7366 10 mg/kg 63 HC-7366 10 mg/kg
GSM8986538 HC-7366 10 mg/kg 80 HC-7366 10 mg/kg
GSM8986539 HC-7366 10 mg/kg 97 HC-7366 10 mg/kg

+ 19 more — browse all 59 samples with per-sample file links →

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